Induction Chemotherapy and Toripalimab for Larynx Preservation in Resectable Laryngeal/Hypopharyngeal Carcinoma (INSIGHT)

January 2, 2022 updated by: Xiayun He, MD, Fudan University

Induction Chemotherapy and Toripalimab Followed by Surgery or Radiotherapy for Larynx Preservation in Resectable Laryngeal/Hypopharyngeal Carcinoma

The aim of this study is to define whether combination of induction chemotherapy and PD-1 inhibitor (Toripalimab) improve the rate of larynx preservation, for patients with resectable laryngeal/hypopharyngeal carcinoma.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Historically, induction chemotherapy could provide a chance of larynx preservation for approximate 60-70% of patients with locally advanced laryngeal/hypopharyngeal carcinoma. Recently, phase I-II clinical studies demonstrated excellent pathological response of induction PD-1 inhibitor with/without chemotherapy for locally advanced head and neck cancer. The aim of this study is to define whether combination of induction chemotherapy and PD-1 inhibitor (Toripalimab) improve the rate of larynx preservation, for patients with resectable laryngeal/hypopharyngeal carcinoma.

Study Type

Interventional

Enrollment (Anticipated)

42

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Yu Wang, M.D.

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200032
        • Recruiting
        • Fudan University Shanghai Cancer Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Pathologically confirmed, resectable locally advanced laryngeal/hypopharyngeal squamous cell carcinoma (T2-4a, N0-resectable N3, M0);
  • Age between 18-75 years;
  • Signed inform consent;
  • Had at least one measurable lesion according to RECIST 1.1 criteria
  • Anticipated overall survival more than 3 months;
  • Satisfactory performance status: ECOG (Eastern Cooperative Oncology Group) scale 0-1;
  • Normal organ function;
  • HBV DNA<500 IU/mL（or 2500 copies/mL）and HCV RNA negative ;
  • Male and no pregnant female, able to adapt birth control methods during treatment.

Exclusion Criteria:

  • Hypersensitivity to Toripalimab, Paclitaxel, Nab-Paclitaxel and Cisplatin;
  • Suffered from malignant tumors, except cervical carcinoma in situ, papillary thyroid carcinoma, or skin cancer (non- melanoma) within five years;
  • Severe, uncontrolled heart disease;
  • Receive vaccine or live vaccine within 28 days prior to signing the informed consent;
  • Equivalent dose more than prednisone 10mg/d or other immunosuppressive treatments within 28 days prior to signing the informed consent;
  • Surgery or trauma within 28 days prior to signing the informed consent;
  • Received other immune checkpoint inhibitors previously;
  • Severe, uncontrolled infections within 28 days of prior to signing the informed consent;
  • Active, known or suspected autoimmune disease; Type I Diabetes, hypothyroidism those only need hormone replacement therapy, vitiligo or inactive asthma who don't need systemic therapy can recruit;
  • History of interstitial lung disease;
  • HIV positive;
  • Hepatitis B surface antigen (HBsAg) positive and HBV-DNA ≥500IU/ml, or 2500cps/ml; Positive HCV RNA;
  • Other diseases which may influence the safety or compliance of the clinical trial, such as mental illness, or their family and society factors;
  • Women of child-bearing potential who are pregnant or breastfeeding.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Induction chemotherapy and Toripalimab

Induction chemotherapy TP regimen combined with Toripalimab for 3 cycles: Toripalimab 240mg d1, Paclitaxel 175mg/m2 d2 or Nab-Paclitaxel 260mg/m2 d2，Cisplatin 25mg/m2 d2-4 q3w.

Response rate of primary tumor is evaluated using laryngoscopy and head and neck MRI after 3 cycles of induction therapy. If ORR of primary tumor is CR/PR, then chemoradiation is conducted, followed by maintenance therapy of Toripalimab for 8 cycles (6 months). Otherwise, surgery is conducted (laryngeal preservation surgery is preferred), followed by adjuvant radiation/chemoradiation and then maintenance therapy of Toripalimab for 8 cycles.
Drug: chemotherapy TP regimen combined with Toripalimab

Induction chemotherapy TP regimen combined with Toripalimab for 3 cycles: Toripalimab 240mg d1, Paclitaxel 175mg/m2 d2 or Nab-Paclitaxel 260mg/m2 d2，Cisplatin 25mg/m2 d2-4 q3w.

Response rate of primary tumor is evaluated using laryngoscopy and head and neck MRI after 3 cycles of induction therapy. If overall response rate of primary tumor is complete response or partial response, then chemoradiation is conducted, followed by maintenance therapy of Toripalimab for 8 cycles (6 months). Otherwise, surgery is conducted (laryngeal preservation surgery is preferred), followed by adjuvant radiation/chemoradiation and then maintenance therapy of Toripalimab for 8 cycles.

Other Names:
  • Cisplatin
  • Paclitaxel or Nab-Paclitaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Laryngeal Preservation rate at 3-month post-radiotherapy
Time Frame: 3-month post-radiotherapy
defined as the absence of any residual disease that would justify salvage total laryngectomy
3-month post-radiotherapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall response rate of induction therapy
Time Frame: 2 weeks after the 3th cycle of induction therapy
Overall response rate of induction therapy evaluated by head and neck MR/CT, laryngoscopy using Recist 1.1 Criteria
2 weeks after the 3th cycle of induction therapy
Overall response rate of treatment
Time Frame: 3 months post-radiotherapy
Overall response rate of treatment evaluated by head and neck MR/CT, laryngoscopy using Recist 1.1 Criteria
3 months post-radiotherapy
Pathological complete response rate of the patients receiving surgical resection
Time Frame: Within 3 weeks after surgery
Pathological complete response rate of the patients receiving surgical resection, evaluated by experienced pathologists
Within 3 weeks after surgery
Major pathologic response rate of the patients receiving surgical resection
Time Frame: Within 3 weeks after surgery
Major pathologic response rate, defined as no more than 10% of residual viable tumor, evaluated by experienced pathologists.
Within 3 weeks after surgery
Overall survival rate at 1 year
Time Frame: One year post-radiotherapy
Overall survival rate at 1 year
One year post-radiotherapy
Overall survival rate at 2 year
Time Frame: Two year post-radiotherapy
Overall survival rate at 2 year
Two year post-radiotherapy
Progression-free survival rate at 1 year
Time Frame: One year post-radiotherapy
Progression-free survival rate at 1 year
One year post-radiotherapy
Progression-free survival rate at 2 year
Time Frame: Two year post-radiotherapy
Progression-free survival rate at 2 year
Two year post-radiotherapy
Laryngeal Preservation rate at 1 year
Time Frame: One year post-radiotherapy
Laryngeal Preservation rate at 1 year
One year post-radiotherapy
Laryngeal Preservation rate at 2 year
Time Frame: Two year post-radiotherapy
Laryngeal Preservation rate at 2 year
Two year post-radiotherapy
Adverse Effect
Time Frame: One year post-radiotherapy
Adverse Effect, evaluated by CTCAE 4.0.03
One year post-radiotherapy

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Laryngeal Preservation rate at 3 month post-radiotherapy by different biomarker subgroups
Time Frame: 3-month post-radiotherapy
Experimental Biomarker Analysis: the relationship with different biomarkers and 3 month laryngeal preservation rate
3-month post-radiotherapy
Overall response rate of induction therapy, by different biomarker subgroups
Time Frame: 2 weeks after the 3th cycle of induction therapy
Experimental Biomarker Analysis: the relationship with different biomarkers and overall response rate of induction therapy
2 weeks after the 3th cycle of induction therapy
Pathological complete response rate by different biomarker subgroups
Time Frame: Within 3 weeks after surgery
Experimental Biomarker Analysis: the relationship with different biomarkers and pathological complete response rate of the patients receiving surgical resection
Within 3 weeks after surgery
Major pathologic response rate by different biomarker subgroups
Time Frame: Within 3 weeks after surgery
Experimental Biomarker Analysis: the relationship with different biomarkers and major pathologic response rate of the patients receiving surgical resection
Within 3 weeks after surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fudan University

Investigators

  • Principal Investigator: Xiayun He, M.D., Fudan Universtiy Shanghai Cancer Center
  • Principal Investigator: Yu Wang, M.D., Fudan Universtiy Shanghai Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 7, 2021

Primary Completion (Anticipated)

December 31, 2024

Study Completion (Anticipated)

December 31, 2025

Study Registration Dates

First Submitted

July 25, 2021

First Submitted That Met QC Criteria

August 2, 2021

First Posted (Actual)

August 6, 2021

Study Record Updates

Last Update Posted (Actual)

January 18, 2022

Last Update Submitted That Met QC Criteria

January 2, 2022

Last Verified

January 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Larynx-IO 1.0
  • 2103232-1 (Other Identifier: IRB of Fudan Univeristy Shanghai Cancer Center)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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